Smallpox (also known by the Latin names Variola or Variola vera) is a highly contagious disease unique to humans. It is caused by two virus variants called Variola major and Variola minor. V. major is the more deadly form, with a typical mortality of 20-40 percent of those infected. The other type, V. minor, only kills 1% of its victims. Many survivors are left blind in one or both eyes from corneal ulceration, and persistent skin scarring - pockmarks - is nearly universal. Smallpox was responsible for an estimated 300-500 million deaths in the 20th century. As recently as 1967, the World Health Organization (WHO) estimated that 15 million people contracted the disease and that two million died in that year.
After successful vaccination campaigns, the WHO in 1979 declared the eradication of smallpox, though cultures of the virus are kept by the Centers for Disease Control and Prevention (CDC) in the United States and at the Institute of Virus Preparations in Siberia, Russia. Smallpox vaccination was discontinued in most countries in the 1970s as the risks of vaccination include death (~1 per million), among other serious side effects. Nonetheless, after the 2001 anthrax attacks took place in the United States, concerns about smallpox have resurfaced as a possible agent for bioterrorism. As a result, there has been increased concern about the availability of vaccine stocks. Moreover, President George W. Bush has ordered all American military personnel to be vaccinated against smallpox and has implemented a voluntary program for vaccinating emergency medical personnel.
Famous victims of this disease include Ramesses V (not confirmed), Mary II of England, Louis XV of France, and Peter II of Russia. Henry VIII's fourth wife, Anne of Cleves, survived the disease but was scarred by it.
After first contacts with Europeans, the death of a large part of the native population of the New World was caused by European-transmitted diseases. Smallpox was the chief culprit. On at least one occasion, germ warfare was used by the British Army under Jeffrey Amherst when smallpox-infected blankets were deliberately distributed to the Ottawa tribe in 1763.
Smallpox is described in the Ayurveda books. Treatment included inoculation with year-old smallpox matter. The inoculators would travel all across India pricking the skin of the arm with a small metal instrument using "variolous matter" taken from pustules produced by the previous year's inoculations. The effectiveness of this system was confirmed by the British doctor J.Z. Holwell in an account to the College of Physicians in London in 1767.
Edward Jenner developed a smallpox vaccine by using cowpox fluid (hence the name vaccination, from the Latin vaca, cow); his first inoculation occurred on May 14, 1796. After independent confirmation, this practice of vaccination against smallpox spread quickly in Europe. The first smallpox vaccination in North America occurred on June 2, 1800. National laws requiring vaccination began appearing as early as 1805. The last case of wild smallpox occurred on September 11th, 1977. One last victim was claimed by the disease in the UK in September 1978, when Janet Parker, a photographer in the University of Birmingham Medical School, contracted the disease and died. A research project on smallpox was being conducted in the building at the time, though the exact route by which Ms. Parker became infected was never fully elucidated.
Transmission is by droplets, and infection in the natural disease will be via the lungs. The incubation period to obvious disease is around 12 days. In the initial growth phase the virus seems to move from cell to cell, but around the 12th day, lysis of many infected cells occurs and the virus will be found in the bloodstream in large numbers. The initial or prodromal symptoms are essentially similar to other viral diseases such as influenza and the common cold - fevers, muscle pain and stomach aches etc. The digestive tract is commonly involved, leading to vomiting. Most cases will be prostrated.
Smallpox virus preferentially attacks skin cells and by days 14-15 smallpox infection becomes obvious. The attack on skin cells causes the characteristic pimples associated with the disease. The pimples tend to erupt first in the mouth, then the arms and the hands, and later the rest of the body. At that point the pimples, called macules, should still be fairly small. This is the stage at which the victim is most contagious.
By days 15-16 the condition worsens and the pimples grow into papules. These then fill up with pus, turning them into pustules. After the appearance of the pustules, the symptoms become vastly different. Route A is if the victim is going to survive the outbreak. The pustule will deflate in time (the duration is variable), and will start to dry up, usually beginning on day 28. Eventually the pustules will dry and start to flake off. Once all of the pustules flake off the patient is considered cured.
If the patient is going to die, an entirely different set of symptoms starts to develop. First, bleeding will occur under the skin, making the skin look charred and black (this is known as black pox). Soon afterwards, bleeding begins in the organs. Death may occur from bleeding, or from loss of fluid and entry of other infectious organisms since the skin and intestine are no longer a barrier, leading to multi-organ failure as with burns.
The virus is tiny but mighty empires have fallen or been weakened because of it.
The first suspected smallpox epidemic is during the Peloponnesian War (431-404 BC) between Athens and Sparta. Because the Spartans had a much greater army, the Athenians were forced to retreat behind the city walls of Athens. From there they hoped to keep the Spartans out, allowing the superior navy of the Athenians to cut off the Spartan supply lines and secure an Athenian victory. But when an Athenian victory seemed within reach, an epidemic broke out in the city, which was tightly packed with people. The epidemic killed Athens's expert seamen and their leader. Leaderless and weakened, the remaining Athenians fought bravely but were still defeated. The loss of the war paved the way for the Macedonians and, ultimately, the Romans.
The next major strike of smallpox did not leave toppled empires behind. Instead, the survivors were so devastated that they created a goddess to honor the virus. The exact date when smallpox entered India is not known, but in 400 A.D. an Indian medical book records a disease that had pustules as one of the symptoms and "the pustules are red, yellow, and white and they are accompanied by burning pain .... the skin seems studded with grains of rice." The full power of smallpox's attack on India is lost to history, but it was bad enough that it was thought to be punishment from a god. In Hinduism there is a goddess named Sitala, who both causes and cures high fever, rashes, hot flashes and pustules. All of these are symptoms of smallpox.
Smallpox did not enter Europe until 581 A.D. Most of the details about the epidemic that followed are lost, probably due to the scarcity of written records and the general lack of social order in the European Dark Ages.
Nowhere did smallpox leave behind as devastating a wake as in the Americas. Popular history has it that the Spanish conquistadores were victorious because they had superior weapons such as the cannon and the musket. But the biological weapons the Spanish soldiers (unwittingly) brought along with them did far more damage.
In 1519 Hernán Cortés landed on the shores of what is now Mexico and was then the Aztec empire. After he landed, one of the most famous coincidences in history took place. The Aztecs were expecting the arrival of a white-skinned god with yellow hair, Quetzalcoatl. Cortes had yellow hair and white skin and thus was received as a god, and tried to rule accordingly. In 1520, another group of Spanish came from Cuba and landed in Mexico. Among them was an African slave who had smallpox. When Cortes heard about the other group he went and defeated them. In the fight, one of Cortes's men contracted the disease. When Cortes returned to Tenochtitlán, he brought the disease with him.
Soon the Aztecs realized that Cortes was not a god and rose up in rebellion. Outnumbered, the Spanish were forced to flee. In the fighting, the Spanish soldier who had smallpox died. After the battle the Aztecs looked on the invaders' bodies for riches and contracted the virus. Cortes would not return until August 1521. In the meantime smallpox was devastating the Aztec population. It killed most of the Aztec army, the emperor, and 25% of the overall population. A Spanish priest described it: "As the Indians did not know the remedy of the disease...they died in heaps, like bedbugs. In many places it happened that everyone in a house died and, as it was impossible to bury the great number of dead, they pulled down the houses over them so that their homes become their tombs." When Cortes did return he found the Aztec army's chain of command in ruins. The soldiers who lived were still weak from the disease. Cortes then easily defeated the Aztecs and entered Tenochtitlán, where he found that smallpox had killed more Aztecs than cannons did. The Aztecs said that they could not walk though the streets without stepping on the bodies of smallpox victims.
The effects of smallpox on Tahuantinsuyu (or Inca empire) were much more devastating. Smallpox spread rapidly in the empire from Colombia before the Spanish invaders first arrived in the empire. It was probably aided by the Inca road system. Within months, the disease had killed the Supa Inca Huayna Capac, his successor, and most of the other leaders. Two of his surviving sons warred for power and, after a bloody and costly war, Atahualpa become the new Supa Inca. As Atahualpa was returning to the capital Cuzco, Francisco Pizarro arrived and through a series of deceits captured the young leader and his best general. Within a few years smallpox claimed between 60% and 90% of the Inca population, with other European plagues weakening them further.
Even after the two mighty empires of the Americas were defeated by the virus, it continued its march of death. North America was next. In 1633 in Plymouth, Massachusetts, the Native Americans were struck by the virus. As it had done elsewhere, the virus wiped out entire populations of Native Americans. It reached Lake Ontario in 1636 and the lands of the Iroquois by 1679, killing millions. The worst single epidemic of smallpox took place in Boston, Massachusetts. From 1636 to 1698, Boston endured six epidemics. In 1721 the hardest hitting epidemic arrived. The entire population fled the city, bringing the virus to the rest of the 13 colonies.
By that time, a treatment for smallpox had finally arrived. It was a process called inoculation, also known as insufflation or variolation. Inoculation was not a new process, having been around for centuries. The Chinese blew powdered smallpox scabs up the noses of the healthy. The patients would then develop a mild case of the disease and from then on they were immune to it. The process spread to Turkey, where an American doctor learned of it. He then told the Royal Society in England where Lady Mary Wortley Montagu learned of it. She began to get other people interested in inoculation. When no one listened, she tried it on her son and daughter, aged 5 and 4 respectively. They both recovered quickly and the procedure was hailed as a success.
In 1721 a new epidemic of smallpox hit London that left the British Royal Family in fear. When they read about the success of Lady Wortley Montagu, they wanted to use inoculation on themselves. The doctors told them that it was a dangerous procedure, so they decided to try it out on some other people first. The victims they used were condemned prisoners. The doctors inoculated all of them and all of them recovered in a couple of weeks. Assured, the British royal family inoculated themselves and reassured the English people that it was safe.
But inoculation still had its critics. Prominent among them were religious persons. Many preachers claimed that smallpox was God's way of punishing people and that inoculation was a tool of Satan. Others more sensibly pointed out that innoculation actually increased the number of smallpox cases in a community and that innoculated people risked spreading the disease to third parties if they moved out of quarantine too early. All this only encouraged Montagu and the others to work even harder. By 1723 inoculations were extremely common in England.
Onesimus  (http://www.tolerance.org/news/article_tol.jsp?id=942)(Oh-NES-ih-mus) was the slave of a Boston preacher in 1721 when smallpox entered Boston via a ship arriving from Barbados. His owner, Cotton Mather asked his slave if he ever had smallpox. Onesimus said, "Yes and no," and explained a technique from his homeland in Africa, thought to be in Sudan. He explained that pus from an infected person was deliberately rubbed into a scratch or cut of a non-infected person, and when successful, the person had immunity. This remedy from an African-American slave was the precursor to inoculations. Cotton Mather, his owner, was also son of a former Harvard University dean  (http://www.countway.harvard.edu/rarebooks/exhibits/waterhouse/), and was waging a campaign of his own to promote the process, although religious resistance to inoculation was very strong. At one point, Cotton Mather was in danger from a crowd that wanted to hang him. After 6 patients died from the procedure, he was called a murderer. But when the population of Boston returned after the end of a smallpox epidemic in 1722, he was an instant hero. Out of the population of Boston, 7% had died from smallpox. Out of the 300 people that chose to inoculate themselves, only 2% died. By 1774 it was considered odd not to get inoculated. Onesimus was later freed by Mather, not for his knowledge and help in combating smallpox, but because Mather considered him to be disobedient.
Even though inoculation was a powerful method of controlling smallpox, it was far from perfect. Inoculation caused a mild case of smallpox which resulted in death in about 2% of cases. Also, it was difficult to administer. Patients had to be locked away while sick to prevent them from transmitting the disease to anyone else. In 1757 a young boy in England by the name of Edward Jenner was inoculated. He suffered from it for a whole month. Even though he recovered later, he was determined to find a better method of preventing smallpox.
At the age of 13, young Jenner was apprenticed to a doctor. He observed that people who had caught cowpox while working with cows were known not to catch smallpox. He assumed a causal connection. The idea was not taken up by Dr. Ludlow at that time.
After Jenner returned from medical school in London, an epidemic struck his home town of Berkeley, England. He advised the local cow workers to be inoculated. The farmers told him that cowpox prevented smallpox. This confirmed his childhood suspicion, and he studied cowpox further.
In 1796 Sarah Nelmes, a local milkmaid, contracted cowpox and went to Jenner for treatment. Jenner took the opportunity to test his theory. He innoculated with cowpox James Phipps the eight year-old son of his gardener. After an extremely weak bout of cowpox, James recovered. Jenner then tried to infect James with smallpox. Nothing happened — the boy was immune to smallpox.
Jenner reported his observations to the Royal Society. The initial reception was cool. Jenner repeated the process with 5 more children, one of them his son Edward. It worked on all of them. After this he was taken seriously, and by 1800 Jenner's work had been published in all of the major European languages. The process was performed all over Europe and the United States. The death rate was close to zero with the process, which became known as vaccination. The Balmis Expedition (1803) carried the vaccine to Spanish America, the Philippines and China under commission of the Spanish Crown.
Benjamin Jesty, a farmer from Yetminster in Dorset (he later moved to and is buried at Worth Matravers) is recorded as observing the two milkmaids living with his family to have been immune to smallpox and then inoculating his family with cowpox to protect them from smallpox some years before Dr. Jenner. This has never been adequately verified, however, and the question of who first developed smallpox inoculation has not been settled to this day.
However, Louis T. Wright  (http://northbysouth.kenyon.edu/1998/health/wright.htm), an African-American and Harvard medical school graduate in 1915, introduced intradermal vaccination for smallpox for the soldiers while serving in the Army during WWI.  (http://www.cs.georgetown.edu/~blakeb/mm/BHM/Spotlight%20on%20Black%20Inventors,%20Scientists,%20and%20Engineers.htm)
Thus it appears that Onesimus, an African, possibly Sudanese slave, Cotton Mather, an American, Edward Jenner, a British country doctor, and Louis T. Wright, a Harvard-educated African American, all from different places and in different times, have contributed in some way toward stamping out one of the plagues of mankind.
Jenner said, "The annihilation of smallpox - the dreadful scourge of the human race - will be the final result of vaccination." Jenner's dream did not go unrealized. Around the world, attempts would be made to annihilate smallpox. For instance, England banned inoculation in 1842 and ordered everyone to get vaccinated instead. In the United States from 1843 to 1855 different states started requiring all students to be vaccinated. Not everyone liked this requirement, however. Many people said that the government was crossing a line by ordering people to get vaccinated. Despite the complaints, the war against smallpox went on and the disease was disappearing quickly in the wealthy countries.
However, in poorer countries such as Somalia and India, vaccines were unheard of and unaffordable. The final effort to attain the noble goal first set by Jenner a century and a half ago would not begin until 1958. In 1958 the Soviet Union called for the eradication of smallpox from the planet. At that point, 2 million people were dying every year from smallpox. In 1967, an international team of doctors was placed under the leadership of the American Donald Henderson.
For their plan to work properly they needed to find the cases of smallpox when they were erupting, so that they could vaccinate everyone who lived close by. This process is known as ring vaccination. This idea was better than to vaccinate everyone who lived on the planet. The latter would require far more resources, which were not available. The team ran into problems right away. They found that 95% of all smallpox victims do not report to the authorities.
Instead of rushing to where smallpox was occurring, they were forced to deploy a network of experts around the world. When the disease emerged, local governments (whether they were willing or not) were rallied to vaccinate everyone in the area.
The project would have failed if not for the sheer heroism displayed by many of the experts involved. All of them knew that failure was not acceptable. The world would never have devoted so many resources to defeat this disease unless it were imperative that smallpox be wiped out.
But smallpox fought tenaciously and did not give up ground easily. In India and Bangladesh, religion and around-the-clock civil wars became huge obstacles. In fear of offending their goddess who was associated with the disease, many Hindus refused the vaccine. Undeterred, the team simply vaccinated them against their will. Civil war ended up being a bigger problem. The nature of war means that troops are often moved from place to place and lodge in crowded tents or barracks, which is the ideal condition for spreading smallpox. The soldiers then spread the disease to villagers, who then spread it out everywhere.
The team's answer to civil war was to vaccinate all the troops, with or without the permission of the generals commanding the armies. The team was placing themselves in grave danger by doing this, and the WHO even told them to stop. Surprisingly, none of the team members were hurt in the process.
Nature, unfortunately, impeded the vaccination team's efforts. Just as the team was on the brink of success, the monsoon rains came, bursting the dams and dikes. The rain flooded the area and forced everyone to flee, once again allowing smallpox to spread. This outbreak took the team a whole year to stop. When this outbreak was gone, smallpox would never again threaten humans.
The last major outbreak of smallpox in Europe was the 1972 outbreak in Yugoslavia. After a pilgrim returned from the Middle East, where he had contracted the virus, an epidemic spread in which 175 people were infected and 35 died. Authorities declared martial law, enforced quarantine and undertook massive revaccination of the population, enlisting help of the WHO and Donald Henderson. In two months, the epidemic was stopped.
The last naturally occurring case of Variola Minor was diagnosed on October 26, 1977. The last naturally occurring case of the more deadly Variola Major was detected two years earlier in November 1975. It had cost a mere 300 million United States dollars to eradicate smallpox.
In 1978 there was evidently an escape from containment in a research laboratory in Birmingham, England. A medical photographer, Janet Parker, died from the disease itself, and the Professor responsible for the unit killed himself. In light of this accident all known stocks of smallpox were destroyed except the stocks at the CDC and the Vector Institute in Koltsovo, Novosibirsk in Siberia, where a regiment of troops guard it. Under such tight control, smallpox would, it was thought, never be let out again. Even though the destruction of virus stocks was ordered in 1993, 1994, 1995, and 1996, they have not yet been destroyed. There apparently remain a number of researchers still wishing to retain the stocks for scientific purposes.
It is also thought that additional stocks of the virus may exist in research collections, the product of the accumulatory nature of microbiologists. Additional collections of the virus almost certainly exist as the result of certain military and biological warfare programs, such as the Soviet State Research Center of Virology and Biotechnology (also known as Vector) labs, which maintained stocks separate from those held by the Moscow Institute for Viral Preparation.
Smallpox scabs were recently found in an envelope in a book on Civil War medicine in Santa Fe, New Mexico.
- CDC smallpox resources (http://www.bt.cdc.gov/agent/smallpox/index.asp)
- Smallpox: A Great and Terrible Scourge (http://www.nlm.nih.gov/exhibition/smallpox/index.html) (2002) U.S. National Library of Medicine Online Exhibition